The genetics of non-insulin dependent diabetes (NIDDM; Type 2 diabetes) will be studied in the Pima Indian Tribe. This collaborative study will include the efforts of molecular geneticists, epidemiologists and clinicians focused on finding the inherited factors which lead to NIDDM. A large number of multiplex families and sib pairs have been identified and collected and some DNA typing and analysis has been carried out already. Initially efforts will be focused on 4 regions of human chromosomes which show some evidence for linkage to NIDDM using sib-pair analysis. In addition, numerous candidate genes will also be surveyed and a systematic survey of the genome will be continued using highly polymorphic microsatellite repeat polymorphisms and restriction fragment length polymorphisms. Data will be analyzed using a number of different linkage analysis approaches including sib-pair analysis, conventional linkage analysis, and also quantitative measures of traits such as obesity, glucose tolerance and insulin resistance. Detection of linkage will be followed by detailed molecular genetic analysis to determine the basis of NIDDM susceptibility. Linkages will also be tested in other populations and ethnic groups.